1. Field of the Invention
This invention relates to certain new and useful N.sup.2 -naphthalenesulfonyl-L-arginine esters and amides, and the pharmaceutically acceptable acid addition salts thereof, which are of especial value in view of their outstanding antithrombotic properties.
2. Description of the Prior Art
In the past, there have been many attempts to obtain new and improved agents for the treatment of thrombosis. Of these, N.sup.2 -(p-tolylsulfonyl)-L-arginine esters are known to be effective in dissolving blood clots. (U.S. Pat. No. 3,622,615, patented Nov. 23, 1971). Also, N.sup.2 -dansyl-1-arginine esters and amides are disclosed in U.S. Application Ser. No. 496,939, now U.S. Pat. No. 3,978,045. A need continues to exist, however, for a highly specific inhibitor on thrombin for the control of thrombosis. SUMMARY OF THE INVENTION
Accordingly, one object of the present invention is to provide a class of N.sup.2 -naphthalenesulfonyl-L-arginine esters, amides and pharmaceutically acceptable acid addition salts thereof.
Another object of the present invention is to provide a class of N.sup.2 -naphthalenesulfonyl-L-arginine esters, amides and pharmaceutically acceptable acid addition salts thereof which are useful in the diagnostic selective determination of thrombin in blood and in drug therapy as antithrombotic agents
Briefly, these objects and other objects of the present invention as hereinafter will become more readily apparent can be attained by N.sup.2 -naphthalenesulfonyl-L-arginine esters and amides of formula (I): ##STR5## or the acid addition salts thereof with a pharmaceutically acceptable acid, wherein R is selected from the class consisting of (1) alkoxy, alkenyloxy, halogenated alkoxy, alkynyloxy and cycloalkoxy, respectively containing not more than 10 carbon atoms, aralkyloxy of not more than 15 carbon atoms, or not more than 10 carbon atoms, tetrahydrofurfuryloxy and alkoxy of not more than 10 carbon atoms substituted with an alkoxy group of not more than 10 carbon atoms, halogen or nitro; (2) ##STR6## wherein R.sub.1 and R.sub.2 are members selected from the class consisting of hydrogen, alkyl, aryl, alkenyl and cycloalkyl, respectively containing not more than 10 carbon atoms, and aralkyl and cycloalkylalkyl, respectively containing not more than 15 carbon atoms, and substituted alkyl containing not more than 20 carbon atoms, said substituent being selected from the class consisting of alkoxy, alkoxycarbonyl, acyl, acyloxy, arylcarbamoyl and N,N-polymethlenecarbamoyl, respectively containing not more than 10 carbon atoms, and carboxy; and ##STR7## wherein Z is a divalent group containing up to 10 or 20 carbon atoms, which consists of more than one group selected from the class consisting of methylene --CH.sub.2 --, monosubstituted methylene ##STR8## wherein R.sub.3 is selected from the class consisting of alkyl, acyl, alkoxy, and alkoxycarbonyl, respectively containing not more than 10 carbon atoms, and carbamoyl, and disubstituted methylene ##STR9## wherein R.sub.4 and R.sub.5 are alkyl groups of not more than 10 carbon atoms, and which may further contain at least one member selected from the class consisting of oxy-O-, thio-S-, cycloalkylene of not more than 10 carbon atoms, imino ##STR10## alkyl-substituted imino ##STR11## wherein R.sub.6 is an alkyl group of not more than 10 carbon atoms, acyl-substituted imino ##STR12## wherein R.sub.7 is an alkyl group of not more than 10 carbon atoms, carbonyl and phenylene ##STR13## which may be arranged in any order and complete the ##STR14## ring together with the said methylene, monosubstituted methylene or disubstituted methylene; and R' is a member selected from the class consisting of 1-naphthyl substituted with 2-, 3-, 4-, 6-, 7-, or 8-dialkylamino, respectively containing not more than 20 carbon atoms, 5-dialkylamino containing 3 - 20 carbon atoms, 2-naphthyl substituted with dialkylamino containing not more than 20 carbon atoms.